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The amelioration of hepatic steatosis by thyroid hormone receptor agonists is insufficient to restore insulin sensitivity in ob/ob mice

dc.creatorALEXANDRO JOSE MARTAGON ROSADO;387520
dc.creatorALEXANDRO JOSE MARTAGON ROSADO;387520es
dc.date2015
dc.date.accessioned2018-10-18T21:51:10Z
dc.date.available2018-10-18T21:51:10Z
dc.identifier.issn19326203
dc.identifier.doi10.1371/journal.pone.0122987
dc.identifier.urihttp://hdl.handle.net/11285/630522
dc.descriptionThyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered. © 2015 Martagón et al.
dc.languageeng
dc.publisherPublic Library of Science
dc.relationhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84927551485&doi=10.1371%2fjournal.pone.0122987&partnerID=40&md5=14f9f5ca9792af91731933c252de5f59
dc.relationInvestigadores
dc.relationEstudiantes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourcePLoS ONE
dc.subjecteprotirome
dc.subjecthormone receptor stimulating agent
dc.subjectliothyronine
dc.subjectsobetirome
dc.subjectthyroid hormone receptor
dc.subjectthyroid hormone receptor agonist
dc.subjecttriacylglycerol
dc.subjectunclassified drug
dc.subject3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid
dc.subjectacetic acid derivative
dc.subjectanilide
dc.subjectglucose 6 phosphatase
dc.subjectglucose blood level
dc.subjectphenol derivative
dc.subjectsobetirome
dc.subjectthyroid hormone receptor
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbody temperature
dc.subjectcontrolled study
dc.subjectglucose blood level
dc.subjectglucose tolerance
dc.subjectglycemic control
dc.subjectinsulin resistance
dc.subjectinsulin sensitivity
dc.subjectliver level
dc.subjectmale
dc.subjectmouse
dc.subjectnonalcoholic fatty liver
dc.subjectnonhuman
dc.subjectob/ob mouse
dc.subjectagonists
dc.subjectanimal
dc.subjectbiosynthesis
dc.subjectdose response
dc.subjectdrug effects
dc.subjectenzyme induction
dc.subjectinsulin resistance
dc.subjectmetabolism
dc.subjectmouse mutant
dc.subjectNon-alcoholic Fatty Liver Disease
dc.subjecttime factor
dc.subjectMus
dc.subjectAcetates
dc.subjectAnilides
dc.subjectAnimals
dc.subjectBlood Glucose
dc.subjectBody Temperature
dc.subjectDose-Response Relationship, Drug
dc.subjectEnzyme Induction
dc.subjectGlucose-6-Phosphatase
dc.subjectInsulin Resistance
dc.subjectMale
dc.subjectMice
dc.subjectMice, Obese
dc.subjectNon-alcoholic Fatty Liver Disease
dc.subjectPhenols
dc.subjectReceptors, Thyroid Hormone
dc.subjectTime Factors
dc.subject.classification7 INGENIERÍA Y TECNOLOGÍA
dc.titleThe amelioration of hepatic steatosis by thyroid hormone receptor agonists is insufficient to restore insulin sensitivity in ob/ob mice
dc.typeArtículo
dc.identifier.volume10
dc.identifier.issue4
refterms.dateFOA2018-10-18T21:51:10Z


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